SGRF (Interleukin-Six, G-CSF Related Factor)/IL-23 (hereafter indicated as “SGRF”) is a novel cytokine cloned by the present inventors based on an EST (Patent number EP1072610, GenBank Accession No. AB030000). Oppmann et al. also isolated this gene using similar methods, reporting it as a novel cytokine (p19/IL-23) that exerts its physiological function by combining with the p40 subunit of IL-12 (Immunity Vol. 13, p 715, 2000). However, to date the physiological function of this gene has been unclear, except for the following: (1) it induces proliferation of CD4+CD45RBlow T cells in mice, and (2) it induces IFN-γ production in human memory T cells. Analysis using IL-12 p40 deficient mice (knockout mice) and research using an antibody against IL-12 p40 has introduced the possibility that functions conventionally attributed to IL-12 could in fact be due to SGRF function.
The present inventors sought effective experimental systems for use in elucidating the functions of the SGRF gene, which were as yet unknown. Genetically modified animals in which SGRF gene allele inactivation lead to lack of SGRF enzymatic activity, or cell lines derived from these genetically modified animals, or ES cell lines can be utilized to elucidate the physiological function of SGRF at both the cellular and whole individual levels. Thus, such animals and cell lines can be used to develop therapeutic drugs to treat diseases associated with the SGRF gene.